Composition for improving intestinal barrier function

Abstract

To provide a composition for improving an intestinal barrier function.SOLUTION: A composition for improving an intestinal barrier function, comprises: one or more compounds selected from the group consisting of Urtica dioica, Perilla frutescens crispa, Mongolian dandelion, golden camellia, Codonopsis pilosula, Styphnolobium japonicum, Cistanche deserticola, Angelica dahurica, Pueraria lobata, Panax ginseng, Hibiscus, Camellia sinensis, Chrysanthemum, Japanese yam, Seaberry, Sambucus nigra, Canarium album, black wolfberry, quinua, Japanese radish, Grifola frondosa, tartary buckwheat, Coprinus comatus, blackberry, and raspberry; and / or one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymoquinone.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a composition for improving the barrier function of the intestinal tract.

Background Art

[0002] The digestive tract such as the intestinal tract is important not only for absorbing necessary nutrients from food but also from the viewpoint of a barrier that separates the outside world from the living body to defend against the invasion of foreign substances such as allergens. When the barrier of the intestinal tract is damaged, harmful substances that should originally be eliminated are absorbed from the intestine, causing various adverse effects. Such a disorder of the intestinal barrier is also called leaky gut, and has been suggested to be associated with various diseases such as food allergy, immune disease, inflammatory bowel disease, irritable bowel syndrome, infectious disease, obesity, diabetes, NAFLD (non-alcoholic fatty liver disease), NASH (non-alcoholic steatohepatitis), metabolic syndrome, cognitive decline, depression, etc. Furthermore, it has also been suggested that a disorder of the intestinal barrier function is associated with various skin diseases. For example, it has been reported that in pediatric atopic dermatitis patients, the severity of symptoms correlates with intestinal permeability, and in psoriasis patients, intestinal permeability is higher compared to healthy individuals (Patent Documents 1 to 6, Non-Patent Documents 1 to 9).

[0003] In recent years, by improving the intestinal barrier function and maintaining a good intestinal state, it is expected to maintain the health of the whole body and skin, treat and prevent diseases, and achieve beauty effects. Therefore, the intake of prebiotics such as oligosaccharides and probiotics such as lactic acid bacteria has been proposed to improve the intestinal barrier function. In addition, for example, it has been shown that the extract of *Bupleurum falcatum* L. has an effect of improving the intestinal barrier function (Patent Document 1). Compounds having gallic acid residues, polyphenols such as flavan-3-ol polymers, nobiletin, quercetin, kaempferol, myricetin (Patent Documents 2 to 4, Non-Patent Documents 1 to 3), and unsaturated fatty acid metabolites (Patent Document 5) have an effect of improving the intestinal barrier function, and it has also been reported that tangerectin has an effect of reducing colitis (Non-Patent Document 4). Furthermore, it has been reported that proline, serine, and threonine have an effect of healing the intestinal mucosa (Patent Document 6), and D-alanine, L-glutamine, glutamine, and whey protein have an effect of improving the intestinal barrier function (Non-Patent Documents 5 to 7). On the other hand, there is still a demand for further substances with a high effect of improving the intestinal barrier function.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Patent Document 6

Non-Patent Documents

[0005]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Non-Patent Document 4

Non-Patent Document 5

Non-Patent Document 6

Non-Patent Document 7

Non-Patent Document 8

Non-Patent Document 9

Summary of the Invention

[0006] The present invention provides a composition for improving the barrier function of the intestinal tract.

[0007] The inventors have surprisingly found that a composition containing specific components can improve the barrier function of the intestinal tract. The present invention is based on these findings.

[0008] According to the present invention, the following inventions are provided. (1) A composition for improving the barrier function of the intestinal tract, comprising one or more selected from the group consisting of Stachys byzantina, Perilla frutescens, Lactuca virosa, Calendula officinalis, Scorzonera humilis, Fagopyrum esculentum, Cichorium intybus, Plantago asiatica, Pueraria lobata, Raphanus sativus, Hericium erinaceus, Fagopyrum tataricum, Hibiscus sabdariffa, Celtis sinensis, Chrysanthemum coronarium, Dioscorea opposita, Seaberry, Equisetum arvense, Phalaenopsis aphrodite, Dioscorea bulbifera, Chenopodium quinoa, Raphanus sativus var. longipinnatus, Grifola frondosa, Fagopyrum dibotrys, Sparassis crispa, Rubus fruticosus, and Rubus idaeus, and / or one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymiquinone. (2) The composition according to (1), comprising one or more selected from the group consisting of Stachys byzantina, Calendula officinalis, and Sparassis crispa. (3) The composition according to (1) or (2) for strengthening tight junctions. (4) The composition according to any one of (1) to (3), which is a food composition.

[0009] According to the present invention, a composition for improving the barrier function of the intestinal tract is provided. Further, the composition of the present invention can also be used to improve the barrier function of the intestinal tract. Detailed description of the invention

[0010] According to one aspect of the present invention, there is provided a composition for improving the barrier function of the intestinal tract. Such a composition comprises one or more selected from the group consisting of perilla, inula britannica, calendula, burdock, lotus root, alisma orientale, euryale ferox, kudzu, carrot, hibiscus, camellia, yarrow, taro, sea buckthorn, centella asiatica, orchid, black cohosh, quinoa, radish, maitake, buckwheat, hericium erinaceus, blackberry, stinging nettle, and raspberry, and / or one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymiquinone. Preferably, it comprises one or more selected from the group consisting of perilla, inula britannica, calendula, burdock, lotus root, alisma orientale, euryale ferox, kudzu, camellia, yarrow, sea buckthorn, centella asiatica, orchid, black cohosh, quinoa, radish, maitake, buckwheat, hericium erinaceus, blackberry, stinging nettle, and raspberry, and / or one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymiquinone. More preferably, it comprises one or more selected from the group consisting of calendula, alisma orientale, yarrow, centella asiatica, orchid, hericium erinaceus, and stinging nettle. Even more preferably, it comprises one or more selected from the group consisting of calendula, hericium erinaceus, and stinging nettle.

[0011] By applying the above composition to a subject, the barrier function of the intestinal tract in the subject can be improved. The improvement of the intestinal tract barrier function is useful for the treatment and / or prevention of various diseases and disorders caused by disorders of the intestinal tract barrier function, such as intestinal diseases like colitis and Crohn's disease, immune diseases like celiac disease, obesity, diabetes, NAFLD, NASH, metabolic syndrome, allergic diseases, cognitive decline, and depression, and for beauty such as improving skin condition.

[0012] The barrier function of the intestinal tract in the present invention means the function of the epithelial cells of the intestinal tract, which separates the external environment from the living body, to restrict the invasion of foreign substances such as allergens and harmful substances. For example, there is a structure called tight junction (TJ) in the intercellular space of intestinal epithelial cells, which contributes to the maintenance of the barrier function of the intestinal tract by controlling the permeation of substances between cells. In addition, there are also reports that sugars and the intestinal flora are involved in the barrier function of the intestinal tract. When the barrier function of the intestinal tract is impaired, undesirable substances can permeate through the intestine and cause adverse effects on the body, such as inflammation (Patent Document 1, Non-Patent Documents 2, 3, 7 to 9).

[0013] The improvement of the barrier function of the intestinal tract in the present invention may include preventing and / or treating the impairment of the barrier function of the intestinal tract as described above, maintaining the intestinal barrier in a normal state, forming / repairing / regulating the function of tight junctions, protecting the intestinal mucosa, promoting the formation of the mucus layer, and the like.

[0014] According to a preferred embodiment of the present invention, a composition for strengthening tight junctions is provided. Such a composition comprises one or more selected from the group consisting of Perilla frutescens, Arctium lappa, Carthamus tinctorius, Pueraria thomsonii, Ziziphus jujuba, Dioscorea opposita, Polygonum hydropiper, Pueraria lobata, Hibiscus sabdariffa, Cinnamomum camphora, Artemisia princeps, Dioscorea esculenta, Rubus sieboldii, Viola mandshurica, Rheum palmatum, Chenopodium quinoa, Raphanus sativus, Grifola frondosa, Fagopyrum tataricum, Hericium erinaceus, Rubus coreanus, Urtica dioica, and Rubus idaeus, and / or one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymiquinone. Preferably, it comprises one or more selected from the group consisting of Perilla frutescens, Arctium lappa, Carthamus tinctorius, Pueraria thomsonii, Ziziphus jujuba, Dioscorea opposita, Polygonum hydropiper, Pueraria lobata, Cinnamomum camphora, Artemisia princeps, Rubus sieboldii, Viola mandshurica, Rheum palmatum, Chenopodium quinoa, Raphanus sativus, Grifola frondosa, Fagopyrum tataricum, Hericium erinaceus, Rubus coreanus, Urtica dioica, and Rubus idaeus, and / or one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymiquinone. More preferably, it comprises one or more selected from the group consisting of Carthamus tinctorius, Dioscorea opposita, Artemisia princeps, Viola mandshurica, Rheum palmatum, Hericium erinaceus, and Urtica dioica. Even more preferably, it comprises one or more selected from the group consisting of Carthamus tinctorius, Hericium erinaceus, and Urtica dioica.

[0015] The strengthening of tight junctions in the present invention means changing the tight junctions so that substances between cells are less permeable, which may be achieved, for example, by forming / repairing / regulating the function of tight junctions.

[0016] The improvement of the intestinal barrier function in the present invention may be achieved by strengthening the tight junctions or may be achieved without strengthening the tight junctions.

[0017] Generally, it is known that the barrier function of the intestinal tract can be evaluated by various methods. For example, it can be evaluated by measuring the lactulose concentration and mannitol concentration in urine after ingestion of mannitol (M), which is an intestinal permeability marker, and lactulose (L), which is a poorly permeable marker, and comparing the lactulose / mannitol (L / M) ratio. It has been reported that the L / M ratio 2.5 to 4 hours after ingestion reflects the barrier function of the small intestine (Patent Document 1). In addition, a method for measuring the barrier function of the intestinal tract by measuring the transepithelial electric resistance (TER) value between Caco-2 cells of the gastrointestinal epithelium has also been reported (Patent Document 1, Non-Patent Documents 2, 3, 8, 9). The barrier function of the intestinal tract in the present invention can be evaluated by known methods, and preferably, it is evaluated based on the measured value of the transepithelial electric resistance value (TER) between Caco-2 cells.

[0018] The composition of the present invention may be applied either in vivo or in vitro. The composition of the present invention is preferably applied to human cells, although not limited thereto.

[0019] The "Perilla" of the present invention means Perilla, a plant species of the genus Perilla in the family Lamiaceae, and includes, for example, those denoted as Perilla frutescens (L.) Britt. The part used is preferably the whole herb or leaves, although not limited thereto. The "Perilla" of the present invention can be used as it is or processed such as dried as needed. If these are commercially available, they may be used as long as they have the object and effect of the present invention.

[0020] The "Moukotanpopo" of the present invention refers to the plant species of Taraxacum in the Asteraceae family, including those denoted as, for example, Taraxacum mongolicum Hand.-Mazz, Taraxacum borealisinense Kitam. The part used is not limited, but preferably the whole plant. The "Moukotanpopo" of the present invention can be used as it is or processed such as dried as needed. If these are commercially sold, they may be used as long as they have the object and effect of the present invention.

[0021] The "Kinkaucha" of the present invention refers to the plant species of Camellia in the Theaceae family, including those denoted as, for example, Camellia chrysantha (Hu) Tuyama. The part used is not limited, but preferably the leaves. The "Kinkaucha" of the present invention can be used as it is or processed such as dried as needed. If these are commercially sold, they may be used as long as they have the object and effect of the present invention.

[0022] The "Hikagesurninjin" of the present invention refers to the plant species of Codonopsis in the Campanulaceae family, which is also denoted as Codonopsis pilosula (Franch.). The part used is not limited, but preferably the roots. The "Hikagesurninjin" of the present invention can be used as it is or processed such as dried as needed. If these are commercially sold, they may be used as long as they have the object and effect of the present invention.

[0023] The "Engju" of the present invention means Sophora japonica L, which is a plant species of the genus Sophora in the legume family. The parts used are not limited, but preferably flowers or flower buds. The "Engju" of the present invention can be used as it is or after being processed such as dried, if necessary. If these are commercially available, they may be used as long as they have the objective effects of the present invention.

[0024] The "Koubakunikujuyou" of the present invention means Cistanche deserticola Y. C. Ma, which is a parasitic plant collected in arid regions in the western regions such as Inner Mongolia in China. The parts used are not limited, but preferably the fleshy stem. The "Koubakunikujuyou" of the present invention can be used as it is or after being processed such as dried, if necessary. If these are commercially available, they may be used as long as they have the objective effects of the present invention.

[0025] The "Yoroigusasa" of the present invention means Angelica dahurica (Fisch.ex Hoffm.) Benth. et Hook.f, including plant species of the genus Angelica in the Apiaceae family. The parts used are not limited, but preferably the roots. The "Yoroigusasa" of the present invention can be used as it is or after being processed such as dried, if necessary. If these are commercially available, they may be used as long as they have the objective effects of the present invention.

[0026] The "Kuzu" of the present invention means Pueraria lobata (Willd.)Ohwi, including plant species of the genus Pueraria in the legume family. The parts used are not limited, but preferably the roots. The "Kuzu" of the present invention can be used as it is or after being processed such as dried, if necessary. If these are commercially available, they may be used as long as they have the objective effects of the present invention.

[0027] The "Korean ginseng" of the present invention means Korean ginseng (Panax ginseng C.A.Mey), which is a plant species of the genus Panax in the Araliaceae family. As the part to be used, although not limited, the root is preferably used. The "Korean ginseng" of the present invention can be used as it is or after being processed such as dried, if necessary. When these are commercially sold, those having the object and effect of the present invention may be used if they can be obtained.

[0028] The "hibiscus" of the present invention means hibiscus, which is a plant species of the genus Hibiscus in the Malvaceae family, and includes those denoted as Hibiscus sabdariffa Linn. As the part to be used, although not limited, the calyx or fruit is preferably used. The "hibiscus" of the present invention can be used as it is or after being processed such as dried, if necessary. When these are commercially sold, those having the object and effect of the present invention may be used if they can be obtained.

[0029] The "tea tree" of the present invention means tea tree (Camellia sinensis), which is also denoted as Camellia sinensis. As the part to be used, although not limited, the leaves are preferably used. The "tea tree" of the present invention can be used as it is or after being processed such as dried, if necessary. When these are commercially sold, those having the object and effect of the present invention may be used if they can be obtained.

[0030] The "garden chrysanthemum" of the present invention means garden chrysanthemum, which is a plant species of the genus Chrysanthemum in the Asteraceae family, and includes those denoted as Chrysanthemum morifolium Ramat. As the part to be used, although not limited, the flower is preferably used. The "garden chrysanthemum" of the present invention can be used as it is or after being processed such as dried, if necessary. When these are commercially sold, those having the object and effect of the present invention may be used if they can be obtained.

[0031] The "Japanese yam" of the present invention means the Japanese yam, which is a plant species of the genus Dioscorea in the family Dioscoreaceae, and includes those denoted as Dioscorea opposita Thunb. The part used is preferably the rhizome, although it is not particularly limited. The "Japanese yam" of the present invention can be used as it is or after being processed such as dried, if necessary. If these are commercially available, those having the object and effect of the present invention may be used.

[0032] The "sea buckthorn" of the present invention means the sea buckthorn, which is a plant species of the genus Hippophae in the family Elaeagnaceae, and is also denoted as Hippophae rhamnoides L. The part used is preferably the fruit, although it is not particularly limited. The "sea buckthorn" of the present invention can be used as it is or after being processed such as dried, if necessary. If these are commercially available, those having the object and effect of the present invention may be used.

[0033] The "European elder" of the present invention means the European elder, which is a plant species of the genus Sambucus in the family Adoxaceae, and is also denoted as Sambucus nigra L. The part used is preferably the fruit (such as pulp and pericarp), although it is not particularly limited. The "European elder" of the present invention can be used as it is or after being processed such as dried, if necessary. If these are commercially available, those having the object and effect of the present invention may be used.

[0034] "Kanran" in the present invention means the plant species of the genus Canarium in the family Burseraceae, including those denoted as Canarium album Raeusch. The part used is not particularly limited, but preferably the fruit (such as pulp and pericarp). "Kanran" in the present invention can be used as it is or after being processed such as dried, if necessary. When these are commercially available, they may be used as long as they have the objective effects of the present invention.

[0035] "Black Goji" in the present invention means the plant species of the genus Lycium in the family Solanaceae, also denoted as Lycium ruthenicum Murray. The part used is not particularly limited, but preferably the fruit (such as pulp and pericarp). "Black Goji" in the present invention can be used as it is or after being processed such as dried, if necessary. When these are commercially available, they may be used as long as they have the objective effects of the present invention.

[0036] "Quinoa" in the present invention means the plant species of the genus Chenopodium in the family Amaranthaceae, including those denoted as Chenopodium quinoa Willd. The part used is not particularly limited, but preferably the spike. "Quinoa" in the present invention can be used as it is or after being processed such as dried, if necessary. When these are commercially available, they may be used as long as they have the objective effects of the present invention.

[0037] "Radish" in the present invention means the plant species of the genus Raphanus in the family Brassicaceae, also denoted as Raphanus sativus L. The part used is not particularly limited, but preferably the seed. "Radish" in the present invention can be used as it is or after being processed such as dried, if necessary. When these are commercially available, they may be used as long as they have the objective effects of the present invention.

[0038] "Maitake" of the present invention means maitake, a mushroom belonging to the genus Maitake of the family Tricholomataceae, and is also denoted as Polyporus frondosus (Dicks.) Fr. [Boletus frondosus Dicks.]. The part used is not particularly limited, but preferably the fruiting body. "Maitake" of the present invention can be used as it is or after being processed such as dried, if necessary. When these are commercially available, those having the object and effect of the present invention may be used if such can be obtained.

[0039] "Tatansoba" of the present invention means tatansoba, a plant species belonging to the genus Buckwheat of the family Polygonaceae, and is also denoted as Fagopyrum tataricum (L.) Gaertn. The part used is not particularly limited, but preferably the seeds. "Tatansoba" of the present invention can be used as it is or after being processed such as dried, if necessary. When these are commercially available, those having the object and effect of the present invention may be used if such can be obtained.

[0040] "Sasakurehitoyotake" of the present invention means sasakurehitoyotake, a mushroom belonging to the genus Sasakurehitoyotake of the family Coprinaceae, and is also denoted as Coprinus comatus. The part used is not particularly limited, but preferably the fruiting body. "Sasakurehitoyotake" of the present invention can be used as it is or after being processed such as dried, if necessary. When these are commercially available, those having the object and effect of the present invention may be used if such can be obtained.

[0041] "Blackberry" in the present invention means the plant species of blackberry (Rubus fruticosus agg) belonging to the genus Rubus in the Rosaceae family. The usable part is preferably the leaf, although it is not limited thereto. The "blackberry" of the present invention can be used as it is or after being processed such as dried, if necessary. If these are commercially available, those having the object and effect of the present invention may be used.

[0042] "Common nettle" in the present invention means the plant species of common nettle (Urtica dioica L) belonging to the genus Urtica in the Urticaceae family. The usable part is preferably the leaf, although it is not limited thereto. The "common nettle" of the present invention can be used as it is or after being processed such as dried, if necessary. If these are commercially available, those having the object and effect of the present invention may be used.

[0043] "Raspberry" in the present invention means the plant species of raspberry belonging to the genus Rubus in the Rosaceae family, including those denoted as Rubus idaeus L and Rubus strigosus. The usable part is preferably the leaf, although it is not limited thereto. The "raspberry" of the present invention can be used as it is or after being processed such as dried, if necessary. If these are commercially available, those having the object and effect of the present invention may be used.

[0044] According to one embodiment of the present invention, an extract produced by using all or part of one or more selected from the group consisting of perilla, sow thistle, calendula, burdock, mulberry, butterbur, stonecrop, kudzu, carrot, hibiscus, camphor tree, yarrow, taro, sea buckthorn, Japanese wild ginger, narcissus, black crowfoot, quinoa, radish, maitake, buckwheat, bracket fungus, blackberry, common nettle, and raspberry.

[0045] The method for producing the above extract is not particularly limited, and it can be extracted according to the methods commonly used in the technical field. Examples of the extraction method include, but are not limited to, hot water extraction method, ultrasonic extraction method, filtration method, reflux extraction method, solvent (e.g., ethanol) extraction method, etc. These can be carried out alone or in combination of two or more methods. Also, in order to obtain a high-purity extract, the extract may be further extracted one or more times by the same method.

[0046] The type of extraction solvent used for producing the above extract is not particularly limited, and any solvent known in the technical field may be used as long as an extract having the object and effect of the present invention can be obtained. Examples of such solvents include, but are not limited to, water, alcohols having 1 to 4 carbon atoms, ethyl acetate, acetone, chloroform, etc., and these may be used in combination of two or more.

[0047] When the above extract is commercially available, it may be used as long as an extract having the object and effect of the present invention can be obtained.

[0048] The blending amount of one or more extracts selected from the group consisting of extracts of Perilla frutescens, Lactuca indica, Calendula officinalis, Scorzonera hispanica, Vicia sativa, Cichorium intybus, Equisetum arvense, Pueraria lobata, Raphanus sativus, Hibiscus sabdariffa, Prunus serrulata, Chrysanthemum morifolium, Dioscorea opposita, Rubus chamaemorus, Urtica dioica, and Rubus idaeus contained in the composition of the present invention can be appropriately determined according to the use.

[0049] The "phenethyl isothiocyanate" of the present invention means a compound represented by the molecular formula C9H9NS (CAS registration number 2257-09-2). The "phenethyl isothiocyanate" of the present invention is contained in cruciferous plants such as cress, wasabi, and broccoli, but is not limited thereto.

[0050] The "thymoquinone" of the present invention refers to a compound represented by C 10 H 12 O2 (CAS registration number 490-91-5). The "thymoquinone" of the present invention is contained in black cumin and the like, but is not limited thereto.

[0051] The blending amounts of phenethyl isothiocyanate and thymoquinone contained in the composition of the present invention can be appropriately determined according to the use.

[0052] The composition of the present invention is not particularly limited, but may be a food composition. When the composition for improving the intestinal barrier function of the present invention or the composition for strengthening the tight junction is used as a food composition, known components (additives) blended in the food composition can be further blended. Such components include, for example, sweeteners, high-sweetness sweeteners (aspartame, sucralose, glycyrrhizin, saccharin, stevia, dulcin, trichlorosucrose, thaumatin, acesulfame potassium, etc.), flavors, colorants, acidulants, antioxidants, emulsifiers, preservatives, stabilizers and the like.

[0053] The food composition of the present invention may be a health functional food such as a nutritional functional food, a food for specified health use, a food with function claims, etc., or a therapeutic diet (that is, one that serves the purpose of treatment, or one prepared based on a menu issued by a doctor and prepared by a dietitian or the like according to it), a diet therapy food, a care food, etc.

Example

[0054] The present invention will be specifically described based on the following examples, but the present invention is not limited to these examples. Unless otherwise specified, the content is expressed in mass%.

[0055] Each sample shown in Tables 1 and 2 below was dissolved in DMSO (manufactured by Fujifilm), and a DMSO solution of each sample was prepared so as to have the concentrations described in Tables 1 and 2 (concentrations confirmed not to exhibit cytotoxicity).

[0056]

Table 1

Table 2

[0057] Cell culture Caco-2 (HTB-37) of human intestinal epithelial cells was purchased from American Type Cell Culture (Rockville, MD, USA) and cultured under the previously reported standard conditions (Non-Patent Documents 2 and 3). The cells were seeded at a density of 0.25×10 6 cells / cm 2 onto the permeable polyester membrane of a Transwell insert (diameter 12 mm, pore size 0.4 μM; Corning, Cambridge Corning, Cambridge, MA, USA), and all tests were performed on the 8th day after seeding. The medium was changed every 3 days for the cells. After culturing for 8 days, each component was added as described below, and the intestinal barrier function was measured.

[0058] Measurement of intestinal barrier function The intestinal barrier function was evaluated by measuring the trans-epithelial electrical resistance (TER) of the Caco-2 monolayer cells of the intestinal epithelium on the Transwell insert based on the descriptions in Non-Patent Documents 8 and 9. The TER of the monolayer cells showed 1000 - 1300 Ω·cm 2 . (Data not shown). The DMSO solution or Control (DMSO) of each prepared sample was added to the apical well, and the cells were incubated for 48 hours. This experiment was based on the previously reported (Non-Patent Documents 2 and 3) that 100 μM of quercetin, myricetin, and quercetin showed a protective effect on the TJ barrier function 48 hours after addition. TER was measured with a Millicell-ERS system (Millipore, Bedford, MA, USA) before the addition of the compound and at 24 and 48 hours after the addition.

[0059] Statistical analysis All values were expressed as mean ± SEM (n = 3 - 4). Also, the ratio of TER at each time point to the initial value before addition was determined, and the TER of each sample was expressed as the ratio to the control at each time point. Statistical analysis was performed using the student t - test. A case with P < 0.05 (vs control) was considered significant.

[0060]

[0061]

Table 3

[0062] Measurement of human intestinal barrier function ​The effects of *Urtica dioica* on the human intestinal barrier function were evaluated. An open-label crossover comparative trial with a placebo control was conducted on 11 healthy men aged 20 to 64 years. The application of *Urtica dioica* was carried out by having the test subjects ingest a test food so that the amount of *Urtica dioica* leaves was 880 mg (equivalent to dry leaves) / day, and the application of the placebo was carried out by having the subjects ingest a control food so that the amount of maltodextrin was the same (i.e., the same amount as the *Urtica dioica* leaves) / day. The ingestion of the test food and the control food was carried out for one week each. Urine samples were collected 6 hours after each subject ingested a mixture of 5 g of lactulose (L) and 1 g of mannitol (M) before and after each one-week ingestion period of the test food or the control food, and the lactulose / mannitol (L / M) ratio in the urine was measured using an LC / MS / MS device (API4000 Qtrap (SCIEX)) under the conditions shown in Table 4 below. The mean value ± standard error of the L / M ratio was calculated. A one-week washout period was provided between the application of the placebo and the application of *Urtica dioica*.

[0063]

Table 4

[0064] The results are shown in Table 5 below.

[0065]

Table 5

[0066] Regarding the L / M ratio, statistical analysis was performed using the paired Student's t-test. A p-value less than 0.05 was judged as a significant decrease in the L / M ratio, and a p-value of 0.05 or more and less than 0.1 was judged as a significant tendency of decrease in the L / M ratio. As a result, in Example 28 (the group to which Japanese nettle was applied), the L / M ratio after application was significantly decreased compared to that before application (p-value = 0.046), but in Comparative Example 4 (the placebo application group), no change was observed in the L / M ratio after application compared to that before application. Also, regarding the L / M ratio after the application of Japanese nettle, when statistical analysis was performed using the paired Student's t-test, its decrease was found to have a significant tendency compared to the L / M ratio after the application of the placebo (p-value = 0.058). From the above results, it was shown that Japanese nettle improves the human intestinal barrier function.

Claims

1. A composition for improving the barrier function of the intestinal tract, comprising one or more selected from the group consisting of Angelica keiskei, Perilla frutescens, Arctium lappa, Calendula officinalis, Scorzonera hispanica, Fagopyrum esculentum, Glycyrrhiza glabra, Glycyrrhiza uralensis, Pueraria thomsonii, Pueraria montana var. lobata, Hibiscus sabdariffa, Cinnamomum camphora, Artemisia princeps, Dioscorea opposita, Rubus chamaemorus, Rubus coreanus, and / or one or more compounds selected from the group consisting of phenethyl isothiocyanate and thymiquinone.

2. The composition according to claim 1, comprising one or more selected from the group consisting of Angelica keiskei, Calendula officinalis, and Pueraria thomsonii.

3. The composition according to claim 1, for strengthening tight junctions.

4. The composition according to any one of claims 1 to 3, which is a food composition.

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